The neurobiology of autism

Abstract

Improving clinical tests are allowing us to more precisely classify autism spectrum disorders and diagnose them at earlier ages. This raises the possibility of earlier and potentially more effective therapeutic interventions. To fully capitalize on this opportunity, however, will require better understanding of the neurobiological changes underlying this devastating group of developmental disorders. It is becoming clear that the normal trajectory of neurodevelopment is altered in autism, with aberrations in brain growth, neuronal patterning and cortical connectivity. Changes to the structure and function of synapses and dendrites have also been strongly implicated in the pathology of autism by morphological, genetic and animal modeling studies. Finally, environmental factors are likely to interact with the underlying genetic profile, and foster the clinical heterogeneity seen in autism spectrum disorders. In this review we attempt to link the molecular pathways altered in autism to the neurodevelopmental and clinical changes that characterize the disease. We focus on signaling molecules such as neurotrophin, Reelin, PTEN and hepatocyte growth factor, neurotransmitters such as serotonin and glutamate, and synaptic proteins such as neurexin, SHANK and neuroligin. We also discuss evidence implicating oxidative stress, neuroglial activation and neuroimmunity in autism.

Figure 1

Genetic and environmental factors that influence intrauterine and early postnatal brain development likely alter neurobiological and neurodevelopmental trajectories that determine the clinical core of ASD.

Figure 2

Multiple genes associated with autism spectrum disorders (ASD) appear to influence neurodevelopment at different stages of prenatal and postnatal life. These genes have specific periods of influence (red solid line) during defined stages of brain development (orange boxes), but their influence may extend to later stages of development including adult life (red broken lines). (Brain development graphic concept based on review by de Graaf‐Peters and Hadders‐Algra. (63))